Water → Methyl 2-(1H-indazol-6-ylamino)-6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyanonicotinate

HRID 515983

反応式

HRID 515983 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:10][C:11]3[N:20]=[C:19](Cl)[CH:18]=[C:17]([C:22]#[N:23])[C:12]=3[C:13]([O:15][CH3:16])=[O:14])[CH:8]=2)[CH:3]=[N:2]1.[NH2:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]1[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35].CCN(CC)CC.O>C1COCC1.CCOC(C)=O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:10][C:11]3[N:20]=[C:19]([NH:24][C@@H:25]4[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]4[NH:31][C:32]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:38])[CH:18]=[C:17]([C:22]#[N:23])[C:12]=3[C:13]([O:15][CH3:16])=[O:14])[CH:8]=2)[CH:3]=[N:2]1

参加物

7

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317650Methyl 2-(1H-indazol-6-ylamino)-6-chloro-4-cyanonicotinate

生成物 1

HCID 67238712Methyl 2-(1H-indazol-6-ylamino)-6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyanonicotinate収率 62%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of methyl 2-(1H-indazol-6-ylamino)-6-chloro-4-cyanonicotinate (115 mg, 0.351 mmol), tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (90 mg, 0.421 mmol) and Et3N (0.073 mL, 0.526 mmol) in THF (1 mL) was stirred at reflux overnight. Water and EtOAc were added to the mixture. The aqueous phase was extracted with EtOAc. The organic phases were combined, washed with H2O and brine, dried over MgSO4, and evaporated. The residue was rinsed with EtOAc to give the title compound as yellow solid (110 mg, 62.0%). 1H NMR (500 MHz, CDCl3) δ ppm 1.00-1.86 (m, 17 H), 3.84 (s, 3 H), 3.91 (br s, 1 H), 4.12 (br s, 1 H), 6.51 (s, 1 H), 6.63 (d, J=8.79 Hz, 1 H), 7.13 (d, J=8.30 Hz, 1 H), 7.97 (s, 1 H), 8.03 (br s, 1 H), 10.71 (br s, 1 H), 12.87 (br s, 1 H).

後処理

  1. temperatureat reflux overnight
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washwashed with H2O and brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. washThe residue was rinsed with EtOAc

出典と根拠

ORDレコード
ord-be4f58b8aa5245ca9b56b8399c911744
出典データセット
uspto-grants-2015_08
特許番号
US09108970B2

関連ノート

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